Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein kinase C has been previously shown both to phosphorylate and to desensitize the ability of the human 5-HT1A receptor to inhibit adenylyl cyclase [Raymond, J. R. (1991) J. Biol. Chem. 266, 14747-14753]. In this study, we examined the effects of short-term treatment with protein kinase A activators on coupling to the inhibition of adenylyl cyclase and on phosphorylation of the human serotonin 5-HT1A receptor in CHO cells that stably express 1200 fmol of receptor/mg of protein. Forskolin induced a concentration- and time-dependent phosphorylation of the receptor that was detectable at 5 min and maximal at 15-30 min with a half-maximal concentration of 10-20 microM. Phosphorylation was also induced by Sp-cAMPS or dibutyryl-cAMP, and blocked by Rp-cAMPS and a pseudosubstrate inhibitor of PKA, but not by heparin (inhibitor of receptor kinase) or sphingosine (inhibitor of PKC). The stoichiometry of phosphorylation induced by forskolin was 1 mol of phosphate per mole of receptor. PKA activators did not induce a measurable desensitization of 5-HT1A receptor-inhibited adenylyl cyclase activity. However, forskolin augmented the desensitization caused by a submaximal concentration of phorbol 12-myristate 13-acetate (300 nM PMA) as evidenced by a rightward shift of the concentration-response curve for 5-HT, and approximately doubled the amount of phosphate incorporated into the receptor by PMA. Forskolin did not augment desensitization or increase the degree of phosphorylation induced by a maximal concentration of PMA (5 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein kinase A induces phosphorylation of the human 5-HT1A receptor and augments its desensitization by protein kinase C in CHO-K1 cells. 772 77

The neuromediator serotonin (5-hydroxytryptamine; 5-HT) has been proposed to play a role in tumor progression. Thus, the aim of the present investigation was to determine whether alterations in the serotonergic system occur in nevomelanocytic tumors. For this purpose, paraffin-embedded biopsies of superficial spreading malignant melanoma (SSM), dysplastic compound nevi (DN) and benign compound nevi (BCN) were characterized with regard to their expression of 5-HT, the 5-HT1A and 5-HT2A receptors, and the serotonin transporter protein (SERT), by immunohistochemical analysis. Melanocytes in the region surrounding the tumor were found to express both the 5-HT1A and 5-HT2A receptors. Tumor cells that immunostained positively for the different serotonergic markers were observed in the suprabasal epidermis of DN tissue and, to an even greater extent, in the case of SSM. Furthermore, some of these latter cells expressed both 5-HT1AR and 5-HT2AR. The level of expression of 5-HT1AR at the junctional area was lower for SSM than for DN or BCN. As the degree of atypia increased, the intensity of tumor cell staining in the dermis for 5-HT1AR and SERT declined. Vessel immunoreactivity for 5-HT2A was more intense in SSM than in BCN tissue. Round-to-dendritic cells that expressed both SERT and 5-HT1AR were seen to infiltrate into the dermal region of the tumor, this infiltration being more evident in the case of DN and SSM. These latter cells were also tryptase-positive, indicating that they are mast cells. Thus, alterations in serotonergic system may be involved in nevomelanocytic tumors and mast cells may play an important role in this connection.
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PMID:Different serotonergic expression in nevomelanocytic tumors. 2428 Nov 11